Coeliac disease is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from infancy on up. Coeliac disease is caused by a reaction to gliadins, a family of related proline and glutamine rich protein in gluten protein, which are found in wheat (and similar proteins of the tribe Triticeae, such as barley and rye). Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein, and the immune system of subjects prone to celiac disease reacts and cross-reacts with the small-bowel tissue, causing an inflammatory reaction. The inflammation subsequently leads to villous atrophy and interferes with the absorption of nutrients, including minerals and fat soluble vitamins. Classic symptoms of coeliac disease include abdominal distension, vomiting, diarrhoea, weight loss (or stunted growth in children), anaemia and fatigue. The strongest and most common response of the immune system to gliadin is directed toward an α2-gliadin fragment of 33 amino acids in length (represented herein as SEQ ID NO: 1) (Shan et al. 2005 J. Proteome Res. 4:1732-1741; Moron et al. 2008; Am. J. Clin. Nut 87(2): 405-14).
The prevalence of clinically diagnosed coeliac disease is 0.05-0.27%. However, population studies from parts of Europe, India, South America, Australasia and the USA indicate that the prevalence may be between 0.33 and 1.06% in children and 0.18-1.2% in adults. There are indications that many people are undiagnosed and have only mild symptoms of gastro-intestinal discomfort.
The only known effective treatment so far is a lifelong gluten-free diet.
A combination of enzymes (prolyl endopeptidase and a barley glutamine-specific cysteine endopeptidase (EP-B2)) that degrade the putative 33-mer peptide epitope of α2-gliadin in the duodenum is disclosed by Siegel M. et al. (2006, Chem Biol 13 (6): 649-58). Piper et al. (2004, J Pharm Exper. Therap 311: 213-219) disclose the use of prolyl-endopeptidase to degrade gliadin peptides. WO 2007/108763 discloses Lactobacillus plantarum strains and a Lactobacillus rhamnosus strain for promoting immunetolerance in coeliac disease or atopic dermatitis. WO 2006/097415 discloses a mixture of 8 sourdough lactic acid bacteria and Bifidobacteria capable of degrading gliadins peptides, such as the fragment 62-75 of the A-gliadin and the epitope 33-mer peptide, thanks to a complementary proteolytic activity between the bacteria. Baked food obtained from these lactic acid bacteria and Bifidobacteria can be used in the diet of a subject suffering from celiac disease. WO 03/028745 discloses strains of lactic acid bacteria with internal peptidases capable of degrading exorphin A5, a 5-mer peptide derived from gluten protein. These strains are capable of lowering the concentration of intestinal pathogenic peptides.